TGF-beta信号通调控淋巴管形成在单纯疱疹病毒性角膜炎治疗中的作用

单纯疱疹病毒性角膜炎（HSK）是世界范围首位的致盲性角膜病，其病程迁延、反复发作、临床治疗手段有限，一直是困扰眼科临床的难题。近十年来新兴的淋巴管研究为HSK的发病机制和治疗提供了新的研究方向。本研究的目的在于探讨HSK急性发作期以及瘢痕期角膜移植术后淋巴管增生与临床转归的关系及其相关分子生物学机制。我们将通过细胞体外实验、基因敲除鼠体内实验以及以HSK急性发作和瘢痕期角膜移植术动物模型为对象的功能性实验，从宏观和微观角度追踪HSK病程中TGF-β信号通路对淋巴管增生的调控规律，并探究干预TGF-β信号通路对HSK急性发作和瘢痕期角膜移植术后排斥反应的治疗效果。基于我们前期的研究结果，本研究将有望为揭开HSK的病理机制开创新的理念，并为其临床预防和治疗提供新的策略。此外，角膜淋巴管的研究也将为其它器官以及全身淋巴系统相关性疾病的发病机理及治疗提供新思路。

Herpes simplex keratitis (HSK) is most common cause of corneal blindness in the world. Its characterisctis, such as long clinical course, frequent recurrency and limited therapeutic strategies, have made it a clinical dilemma. Lymphatic research, a novel field with rapid development during the past decade, brings a new research direction to the immunology related to HSK. The purpose of current study is to investigate the relationship between lymphangiogenesis (the formation of new lymphatic vessels) and pathogenesis of HSK . We plan to set up in vitro cell molecular assay, in vivo study with conditional knockout mouse and functioanl studies with HSK mouse model and corneal transplantation model in order to investigate the role of TGF-βsignaling on lymphangiogenesis, and observe the therapeutic effect of TGF-βsignaling via controling corneal lymphangiogenesis in HSK. Based on our previous results, we anticipate that the current study can provide new concept to the pathological mechanism on HSK, and provide a new strategy to treat this clinical condition. Additionally, the current study will also benefit the research and treatment of lymphatic diseases in other organs.